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Renal and metabolic effects of insulin lispro in type 2 diabetic subjects with overt nephropathy

Piero Ruggenenti1, Claudio Flores, Claudio Aros

  • 1Clinical Research Center for Rare Diseases Aldo & Cele Daccò, Ranica, Mario Negri Institute for Pharmacological Research, Bergamo, Italy. manuelap@marionegri.it

Diabetes Care
|January 28, 2003
PubMed
Abstract

Insights

Insulin lispro prevents glomerular hyperfiltration in type 2 diabetes patients with nephropathy, potentially by antagonizing insulin-like growth factor 1 (IGF-1). This offers a new perspective on managing diabetic kidney disease progression.

Area of Science:

  • Nephrology
  • Endocrinology
  • Pharmacology

Background:

  • Diabetic nephropathy is a major complication of type 2 diabetes.
  • Glomerular hyperfiltration, mediated by insulin-like growth factor 1 (IGF-1), contributes to nephropathy progression.
  • Rapid-acting insulin analogs like lispro are commonly used for postprandial glucose control.

Purpose of the Study:

  • To investigate whether insulin analog lispro antagonizes the renal effects of IGF-1.
  • To assess the impact of lispro on glomerular hyperfiltration in patients with type 2 diabetes and macroalbuminuria.

Main Methods:

  • A randomized crossover study was conducted with 11 type 2 diabetic patients exhibiting macroalbuminuria.
  • Renal and metabolic responses to regular insulin and lispro were compared under euglycemic clamp conditions before a standard meal.
  • Glomerular filtration rate (GFR), renal plasma flow, and metabolic parameters were monitored.

Main Results:

  • Insulin lispro significantly altered postprandial glomerular filtration rate (GFR) trends compared to regular insulin.
  • Postprandial GFR changes after lispro were negatively correlated with plasma insulin concentration.
  • Lispro prevented the increase in renal plasma flow and decrease in renal vascular resistance observed with regular insulin.
  • Postprandial blood glucose levels were significantly lower with lispro, despite comparable insulin profiles.

Conclusions:

  • In type 2 diabetes with overt nephropathy, insulin lispro effectively prevents glomerular hyperfiltration.
  • Lispro may counteract the renal effects of hyperglycemia through mechanisms potentially involving IGF-1 antagonism.
  • These findings suggest a role for lispro in mitigating diabetic kidney disease progression.

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